The rat and mouse have been chosen as the central animal models for in vivo and many in vitro studies in this program project. Rats and mice are uniquely suited for these investigations because of the large data base on cardiac transplants and atherosclerosis that the participants in this program project have already accumulated and that are available in the literature. The Animal Core has been functioning for five years as a common resource for in vivo models of AGA. The major benefit of having an Animal Core is the optimized use of animals by sharing material from control and experimental cardiac transplants that are performed with a uniform technical expertise. This has promoted the comparison of vascular lesions that develop in all of the models used by different projects. The role of the animal core in facilitating collaborative use of critical animal models as they are developed. One example of this is the use of various knock out mice. After the importance of iNOS was established in the rejection of B 10.A cardiac allografts to C57BL/6 recipients with iNOS knock outs, this strain combination was expanded for use with eNOS, von Willebrand factor and P-selectin knock outs by Dr. Lowenstein, and Granzyme B knock outs by Dr. Rosen. A uniform method of immunosuppression was adopted (treatment with monoclonal antibodies to CD4) to prevent acute rejection. As a result common controls could be used and comparisons among experimental groups could be made for end points of common interest, such as cellular infiltrates, endothelial injury and release of von Willebrand factor. Animal models of cardiac allografts will continue to be used in all of the proposed projects. Three projects will make use of mice and rats and two projects will use primarily just mice or rats.